Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Anti-Cancer Effect of the Combination of Thiacremonone and Docetaxel by Inactivation of NF-κB in Human Cancer Cells

  • Ban, Jung-Ok (College of Pharmacy, Chungju National University) ;
  • Cho, Jin-Suk (College of Pharmacy, Chungju National University) ;
  • Hwang, In-Guk (College of Agriculture, Life and Environments Sciences, Chungju National University) ;
  • Noh, Jin-Woo (College of Agriculture, Life and Environments Sciences, Chungju National University) ;
  • Kim, Wun-Jae (Departments of Urology and Biochemistry (SCB), College of Medicine, Institute for Tumor Research, Chungju National University) ;
  • Lee, Ung-Soo (Department of Food and Biotechnology, Chungju National University) ;
  • Moon, Dong-Cheul (College of Pharmacy, Chungju National University) ;
  • Jeong, Heon-Sang (College of Agriculture, Life and Environments Sciences, Chungju National University) ;
  • Lee, Hee-Soon (College of Pharmacy, Chungju National University) ;
  • Hwang, Bang-Yeon (College of Pharmacy, Chungju National University) ;
  • Jung, Jae-Kyung (College of Pharmacy, Chungju National University) ;
  • Han, Sang-Bae (College of Pharmacy, Chungju National University) ;
  • Hong, Jin-Tae (College of Pharmacy, Chungju National University)
  • Published : 2009.10.31
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Abstract

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

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References

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